This invention relates to the controlled release of a biologically active compound to an aqueous medium where the active compound participates in altering a target compound--e.g., in vivo release of a hormone to the blood stream of a mammal where it regulates the metabolism of a target metabolite.
Various systems for controlled release of a biologically active compound to an aqueous medium are known. For example, Folkman et al. U.S. Pat. No. 4,164,560, and Hsieh et al. U.S. Pat. No. 4,357,312 describe polymeric bodies that can be implanted, in vivo, to provide controlled sustained release of drugs. Such systems generally provide release at a constant rate over a long period of time.
The amount of a drug such as insulin that is needed may vary widely during the course of the day and, in many controlled release situations, it is desirable to provide higher levels of the active compound when it is specifically needed, and to conserve the active compound at other times. Specifically, insulin is required in relatively large doses immediately after a meal, and it is possible that some of the serious long-term complications that diabetics suffer result from an inability to regulate the amount of insulin being administered, with the result that, for a significant period of each day, the patient experiences either too much insulin or a build-up of metabolites from too little insulin.
Folkman et al. USSN No. 290,729, filed Aug. 6, 1981, discloses one approach to this problem in which magnetically responsive particles are included within the polymer matrix, and a temporary increase in the release of a drug such as insulin is effected by subjecting the polymer matrix to an oscillating magnetic field. Another approach involves the use of pancreatic beta cells encapsulated in a biocompatible membrane and implanted subcutaneously. Lym, Science (1980) 210:908. The normal feedback mechanism of the cells controls the amount of insulin they provide.
Lossef U.S. Pat. No. 4,364,385 discloses release of insulin contained within a semipermeable membrane that includes glucose oxidase and catalase. Glucose levels outside the membrane alter the charge of the membrane via glucose oxidase activity, thus changing the membrane's permeability to insulin.